Proposed research is directed toward an understanding of mechanisms which operate in two areas which contribute to hemostasis. First is the development of fibrin clot structure. Release of A-peptides gives monomer fibrins, fA, and when these appear in a free form, association. The release of B-peptides gives fAB, whose distribution in protofibrils is responsible for lateral interaction when clots develop within approximately an hour. The rate of production of fA and the relative rate of roduction of fAB determine the structure and characteristics of an initial protofibril network which is dominant: Its elements accumulate free fibrin and fibrin as it is produced and determine mature network characteristics, such as mean mass/length ratio. An objective is a more detailed specification of the structure of the initial protofibril network, particularly of the relationships between the distribution of protofibril segments which are capable of lateral interaction and the mode in which they appear in the network. Reagents such as thrombin, hirudin and polyethylene glycol affect enzamatic and association reactions differentially. Studies of the manner in which these perturb normal clotting time leads to model responses to which the effects of other agents, for example calcium and clinically important agents such as heparin and protamine, can be compared. An objectiv is determination of effects by comparison. Second is the maintenance of platelet response and structural and metabolic integrity. Using ADP-induced aggregation response, fibrinogen appears mainly to be involved in the expression of response and albumin in the maintenance of integrity. Relationships between response and platelet concentration and environmental refractive index, necessary for a specific interpretation of the roles of plasma constituents, were obtained. An objective is development of a comprehensive model relationship.